The objective of this proposal is to seek support for the purchase of a matrix-assisted laser desorption ionization-time-of-flight mass spectrometer (MALDI-TOF MS; PE Biosystems Voyager DE-STR). No MALDI-TOF MS is presently available at the University of Rochester. There is, however, a need for a MALDI-TOF MS, as demonstrated by the ten major users, all of whom are funded by NIH. M.. W. Anders (Principal Investigator) uses mass spectrometry routinely in his research on chemical metabolism and bioactivation; his present project involves the use of MALDI-TOF MS to characterize xenobiotic-modified glutathione transferases. Other major users propose to use MALDI-TOF MS to study signal transduction in the cardiovascular system (B. Berk), for the characterization of oxidized lung surfactant proteins and lung pollutant defense (J. Finkelstein; B. Stripp), to characterize posttranslational modifications of tubulins (M. Gorovsky), to study phosphorylation and palmitoylation of receptor proteins (P. Hinkle), to study the molecular mechanism of binding reactions mediated by protein surface loops (S. Koide), to characterize the successful incorporation of new nucleotides and new backbones into DNA and RNA strands and to determine their stability (E. Kool), to understand the mechanisms by which cyclooxygenase-derived products facilitate photocarcinogenesis (A. Pentland), and to determine how mucin-glycoprotein biosynthesis is regulated by examining the mechanisms that control the initiation of O- glycosylation (L. Tabak). The MALDI-TOF MS will be incorporated into the Protein Chemistry Core Facility, and a technician will be responsible for instrument operation and sample analysis. A Mass Spectrometry Committee has been named that will provide long-term guidance about the use the instrument and its integration into the Protein Chemistry Core Facility. The institutional commitment includes the provision of technical support and cost-sharing of service contracts.